Pathologia

Pathogenetic features of iNOS expression in the basal magnocellular nucleus of rats against the background of experimental neurodegeneration

M. V. Danukalo — 2024-08-30

Aim. To characterize the features of iNOS expression in neurons of the basal magnocellular nucleus against the background of nitrosative stress during experimental colchicine-induced neurodegeneration.

Materials and methods. The study was conducted on 30 male Wistar rats. At the first stage of the experiment, cognitive impairments were modeled in rats (n = 10) by intracerebroventricular injection of colchicine, and compared with sham-operated and intact animal groups, the validity of the model was demonstrated using an 8-arm radial maze LE760 (PanLab Harvard Apparatus, Spain). Subsequently, the animals were euthanized with sodium thiopental, and the brain was removed for histological, immunofluorescence, and biochemical analyses.

Results. It was found that intracerebroventricular injection of colchicine compared to intact and sham-operated animals leads to disruption of histoarchitecture in the basal magnocellular nucleus of rats with a significant decrease in the Nissl substance area in neurons by 47.3 % and 35.9 %, respectively. At the same time, the level of nitrites in the brain homogenates of animals with experimental neurodegeneration exceeded the comparison groups almost 10 times (intact) and 7 times (sham-operated rats). Meanwhile, immunofluorescence investigation of iNOS expression in the basal magnocellular nucleus of rats with intracerebroventricular colchicine administration, compared to intact and sham-operated animals, revealed a significantly higher value of corrected total cell fluorescence by 22.7 % and 45.3 %, respectively. Simultaneously, it was established that experimental colchicine-induced neurodegeneration is accompanied by a significantly greater number of iNOS⁺ cells in the basal magnocellular nucleus compared to control groups.

Conclusions. Intracerebroventricular injection of colchicine to experimental rats is accompanied by morphological signs of neurodestruction in the basal magnocellular nucleus against the background of nitrosative stress. iNOS expression in rats after intracerebroventricular colchicine administration in the cells of the basal magnocellular nucleus is characterized by a higher enzyme content compared to intact and sham-operated animals. The area of immunopositive cells between experimental groups does not change statistically. Intracerebroventricular administration of colchicine to experimental rats is accompanied by an increase in the number of immunopositive cells for iNOS in the basal magnocellular nucleus.

The combined effects of ursodesoxycholic acid and quercetin on liver health and cardiac function in patients with non-alcoholic fatty liver disease and atrial fibrillation

O. B. Teslenko — 2024-08-30

Non-alcoholic fatty liver disease (NAFLD) or due modern nomenclature – metabolic dysfunction-associated steatotic liver disease (MASLD) and atrial fibrillation are interconnected health problems that require reassessment of treatment strategies to address their common underlying causes. Lifestyle changes and pharmacotherapy are used to manage NAFLD, while treatment for atrial fibrillation focuses on anticoagulation and rhythm control.

Aim. To evaluate the efficacy of combining ursodesoxycholic acid and quercetin with standard treatment to improve liver health and heart function in patients with non-alcoholic fatty liver disease and atrial fibrillation.

Material and methods. A prospective, randomized controlled trial was conducted on patients with NAFLD and atrial fibrillation at two hospitals from January 2020 to December 2023. The study involved 127 patients who were divided into three groups: standard treatment, standard treatment + ursodesoxycholic acid (UDCA), and standard treatment + UDCA + quercetin.

Results. The average age and sex distribution were similar among the three groups, suggesting that the randomization process successfully balanced the demographic characteristics. Paroxysmal atrial fibrillation was the most common form in all groups, followed by persistent atrial fibrillation and permanent atrial fibrillation, with no statistically significant differences between the groups. The body mass index was comparable across all three groups as well. The results showed a decrease in liver stiffness in all groups, with groups 2 and 3 showing the most significant improvements. Fibrosis stages also shifted after treatment, with group 3 showing a marked reduction in progressive fibrosis. Groups 2 and 3 also showed significant reductions in steatosis levels, with an increase in the proportion of patients without steatosis. Left atrial diameter decreased in all groups, with group 3 showing the most significant reduction. Left ventricular ejection fraction improved in all groups, with the most significant increase in group 3. Group 3 also showed improvements in diastolic filling and left ventricular filling pressure. Overall, the combined treatment regimen in group 3 appeared to have the most favourable effects on liver and cardiac health.

Conclusions. The addition of UDCA and quercetin to standard treatment regimens for NAFLD and atrial fibrillation shows promising improvements in liver health and cardiac function.

Diagnostic accuracy of endoscopic optical evaluation and forceps biopsy in comparison with pathohistological findings of colorectal laterally spreading tumors

V. S. Tkachov — 2024-08-30

Following the principles of image-enhanced endoscopy and using standardized endoscopic classifications, it is possible to predict the morphological diagnosis of colorectal neoplasms with high accuracy. The large size and uneven surface of lesion significantly complicates a thorough examination, and routine biopsy is still widely practiced, despite its drawbacks. This makes it necessary to compare the results of optical and forceps biopsy and determine the expediency of performing the latter for different types of colorectal laterally spreading tumors (LST).

Aim. To compare the pit and vascular pattern, determined endoscopically, with histopathological findings in LST, with the calculation of the diagnostic accuracy of optical evaluation and forceps biopsy. To ascertain the relationship between lesion size, morphological type, and the presence of malignant changes.

Materials and methods. 80 LST ≥20 mm were included in the study. Expert image-enhanced endoscopy with NBI and utilizing Paris, Kudo, JNET and Hiroshima classifications was employed for optical evaluation and stratification of lesions. Target forceps biopsy was obtained from areas showing the most progressive changes. The data from optical biopsy and the pathohistology of forceps biopsy specimens were compared with the results of the pathohistological findings of removed LST. Statistics were calculated in the Statistica 13.

Results. Group 1 comprised 30 patients with non-granular type LST, while group 2 consisted of 50 patients with granular type LST. The median diameter was 20 mm (IQR, 20; 25) and 40 mm (IQR, 25; 50), adenocarcinoma loci were found in 10 % and 32 % in the first and second groups, respectively. Correlations between lesion localization and LST subtype were assessed, as well as between the presence of malignant changes and the size and morphological type of the lesions. Comparative indicators of sensitivity (80.0 % / 81.8 % in the first and 76.7 % / 80.0 % in the second group), diagnostic accuracy (93.3 % for both methods in the first and 84.0 % / 86.0 % in the second group), and also predictive values were revealed for optical evaluation / forceps biopsy, respectively. The specificity was identical and amounted to 100 % in the first and 95 % in the second group. In all cases, p < 0.01.

Conclusions. Mixed type LST-G lesions occur more often in the rectum, whereas flat elevated LST-NG lesions – in the transverse colon. The presence of adenocarcinoma correlates with the morphological type of tubulovillous adenoma and the larger size of the tumor; larger LSTs are more frequently tubulovillous adenomas. Optical and forceps biopsies demonstrate higher accuracy for non-granular types of LST compared to granular types. Forceps biopsy does not confer any advantages over optical biopsy and is not recommended for routine use.

The effect of polymorphism of the angiotensin-converting enzyme gene on the course of arterial hypertension in combination with type 2 diabetes and the effectiveness of antihypertensive therapy

O. V. Al-Trawneh — 2024-08-30

The aim of the work is to determine the influence of angiotensin-converting enzyme (ACE) gene polymorphism on the course and effectiveness of antihypertensive therapy using the ACE inhibitor lisinopril and the beta-blocker carvedilol in patients with comorbidity of arterial hypertension and type 2 diabetes.

Materials and methods. The study was carried out based on the Department of arterial hypertension and kidney disease of the L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine. The study included 106 patients with arterial hypertension of the 2^nd degree, stage II and diabetes mellitus type 2, the average age was 54.3 ± 5.3 years. All patients were divided into three groups. The first group consisted of 48 patients with the A/A genotype of the polymorphic marker 2350 A/G of the angiotensin-converting enzyme gene, the second group included 22 patients with the A/G genotype, and the third group included 36 patients with the G/G genotype. DNA of peripheral blood leukocytes was used to study the single-nucleotide polymorphism of marker 2350 A/G of the angiotensin-converting enzyme gene. A combination of lisinopril and carvedilol was used as antihypertensive therapy.

Results. Direct correlations were established between the presence of A/G and G/G genotypes of the single-nucleotide polymorphism 2350 A/G of the angiotensin-converting enzyme gene with an increased body mass index (p < 0.001), higher levels of systolic and diastolic blood pressure (p < 0.001), with an increased level of fasting blood glucose (p < 0.05), the HOMA-IR (p < 0.05), an increased level of low-density lipoproteins (p < 0.05) and triglycerides of the blood (p < 0.05). Positive correlations of the specified polymorphisms with an increase in the mass index of the myocardium of the left ventricle were also established (p < 0.001). As a result of the treatment, a significant decrease in blood pressure, both systolic and diastolic, was observed in all patients (p < 0.001). A statistically significant decrease in the left ventricular myocardial mass index was found (p < 0.001) in all groups of patients. At the same time, the reduction of left ventricular myocardial hypertrophy was statistically more pronounced in patients with genotype A/A than in patients with genotypes A/G and G/G (p < 0.05). In three groups of patients, a significant (p < 0.05) decrease in BMI was observed under the influence of diet therapy and drug treatment. Among the comparison groups of patients, the statistically most significant decrease of this indicator in treatment dynamics was found in individuals with the A/A genotype. A significant decrease in fasting blood glucose levels, HOMA-IR insulin resistance index, and markers of atherogenic dyslipidemia was revealed in both patients with the A/A genotype and those with the A/G and G/G genotypes (p < 0.05). The decrease in the level of insulin resistance (IR) in patients after treatment in all studied groups had positive correlations with the decrease in indicators of left ventricular hypertrophy (LVH) (p < 0.05). Positive correlations were also observed in patients of all observation groups between a decrease in body mass index (BMI) after treatment and a decrease in LVH (p < 0.05). There were no statistically significant differences between the studied parameters between the A/G and G/G groups, both before and after treatment. This confirms that the G allele of the polymorphic marker 2350 A/G of the ACE gene is associated with the development of hypertension and LVH.

Conclusions. The therapy with the combination of lisinopril and carvedilol in patients with hypertension and type 2 diabetes contributed to the effective reduction of blood pressure in three groups of patients. It was established that patients with genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene had more pronounced hypertrophic changes of the myocardium than patients with genotype A/A before the start of treatment. Antihypertensive therapy was the most effective in reducing myocardial hypertrophy in patients with the A/A genotype of the polymorphic marker 2350 A/G of the ACE gene. It was found that the presence of genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene can be used as a predictor not only of the development of LVH but also of metabolic disorders associated with increased BMI, glycemia and insulin resistance, expressed by shifts in atherogenic dyslipidemia in patients with comorbid hypertension and type 2 diabetes. It was established that a decrease in the degree of LVH accompanied by a decrease in IR and BMI. It has been proven that the use of antihypertensive therapy with the use of carvedilol and lisinopril in the treatment regimen in patients with unfavourable genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene is effective and contributes to marked regression of LVH. It was determined that patients with the AA genotype of the polymorphic marker 2350 A/G of the ACE gene have the greatest prerequisite for the effective reduction of LVH after treatment, which was considered a favourable prognostic sign.

US-individualized infusion therapy in geriatric patients after emergency abdominal surgery: effect on the development of acute kidney injury

N. V. Momot — 2024-08-30

In most elderly patients, prescribing the necessary volume of infusion therapy for the prevention of prerenal acute kidney injury (AKI) requires individualization. It is considered that ultrasound examination of the inferior vena cava (IVC) can be an effective additional method of assessing volemia in this category of patients.

The aim is to determine the effectiveness of infusion therapy based on ultrasound of the inferior vena cava for the prevention of AKI in geriatric patients after urgent abdominal surgery.

Materials and methods. A prospective single-center study included 50 patients (74.5 (68.0; 81.0) y. o.), divided into 2 groups: group A (n = 25, infusion therapy based on ultrasound of the IVC); group B (n = 25, infusion therapy based on changes in hemodynamic parameters and diuresis). The diameter of the IVC was determined using ultrasonography (ultrasound probe CN-6, SIEMENS, Acuson Antares), hemodynamic parameters were assessed using esCOO technology (Vismo PVM-2701K monitor, Nihon Kohden, Japan). The KDIGO classification was used to determine the presence and stage of AKI. Statistical analysis was performed using the program Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J).

Results. The daily volume of infusion therapy in group A was 150 ml more than in group B (p = 0.049). Group A patients had 1.2 times higher CI (p = 0.016), by 6 mm Hg higher MAP (p = 0.012), 1.3 times greater SV (p < 0.001) than patients in group B. Also, they required 2 times less use of vasopressors (p = 0.026) and 2.8 times less use of diuretics (p = 0.008). Correlation between SV, CI, MAP and IVC diameter was weak but significant (r = 0.35, r = 0.25, r = 0.29, respectively, p ˂ 0.05). The incidence and severity of AKI did not differ between the study groups. In group A, the intensive care unit stay was 42 (35; 102) hours versus 80 (48; 176) hours in group B (p = 0.028) and survival rate was 88 % versus 40 %, respectively (p = 0.004).

Conclusions. Infusion therapy based on ultrasound of the inferior vena cava may be effective in geriatric patients after urgent abdominal surgery in the intensive care unit. The assessment of volemia based on the determination of the maximum diameter of the IVC is a good additional criterion for the individualization of the volume of postoperative infusion therapy aimed directly at the optimization of systemic hemodynamics and indirectly at the prevention of AKI.

Influence of diabetes on the character of changes of resorption and repair processes in the parodontium and mandibular tissues after tooth extraction

A. V. Abramov — 2024-08-30

Today, diabetes mellitus (DM) represents a problem on which the attention of endocrinologists, general practitioners, and dentists is focused. Early pathological changes, which manifest themselves in the oral cavity, determine the relevance and social significance of this pathology, because dentists are usually the first to diagnose disorders of carbohydrate metabolism based on the results of the analysis of specific complaints and typical clinical symptoms of damage to the mucous membrane and periodontal tissues.

The aim of the work is to find out the pathogenetic characteristics of the reparative component of the post-extraction alveolar socket depending on the time after tooth extraction in experimental diabetes.

Materials and methods. In total, 120 sexually mature (age 8–10 months) male Wistar rats, divided into 8 groups of 15 animals each, were used for research. Complex immunohistological, radiographic and biochemical studies were used for the purpose of detailed analysis of the features of the course and mechanisms of development of complications after tooth extraction against the background of DM. In order to assess the state of the innate link of local immunity, the specifics of the course of repair processes at different times of the post-extraction period, the levels of cell proliferation (by expression of Ki-67) and the concentration and content of CD68-positive macrophages in the mucous membrane were determined immunohistochemically. In order to determine the state of the bone tissue of the dental and jaw apparatus and the levels of mineralization of the hard tissues of the molars in the animals of the experimental groups, radiovisiographic images of the right half-mandible were analyzed with determination of the radiographic density.

Results. Analysis of proliferative-reparative relationships showed almost no macrophages and very low proliferative activity in the intact periodontium, on the other hand, in DM, initial significant diffuse infiltration by CD68-immunopositive cells with high levels of Ki-67 expression was found. Analysis of X-ray images of the half-mandible revealed that induced DM in rats, even without prior surgical intervention, led to the intensification of resorption processes in bone tissue, which was evidenced by a decrease in radiographic density in the root region of the 1^st molar and intraalveolar bone membranes of all three lower molars.

Conclusions. In the intact periodontium, there are almost no CD68-immunopositive macrophages and very low proliferation activity in the periodontal soft tissues. In experimental diabetes, on the contrary, initial significant diffuse infiltration by CD68-immunopositive macrophages with high proliferative activity of most fibroblasts is determined. Induced diabetes in rats, even without prior surgical intervention, leads to increased resorption processes in the bone tissue of the mandible and long-term prolongation of the inflammatory process after tooth extraction.

Peri-implant osteogenesis on alumina-coated titanium implants in rat femur: morphological and elemental analysis of implant surfaces

O. O. Bondarenko — 2024-08-30

Peri-implant bone tissue regeneration involves complex processes that are not yet fully understood at the cellular and molecular levels, leaving significant gaps in our knowledge that require further investigation.

Aim. The study aimed to compare peri-implant osteogenesis on titanium femoral implants with alumina composite coatings applied by different methods to conventional titanium implants in an animal model.

Materials and methods. Implants underwent sandblasting with silicon carbide, plasma torch treatment, and coating with titanium, corundum, sprayed titanium wire, or hydroxyapatite, resulting in seven different surfaces. 105 female Wistar rats received implants in their right femurs and were divided into 7 groups based on implant type and exposure duration (1, 2, or 4 weeks). Implant fragments were analyzed using scanning electron microscopy and energy dispersive X-ray spectroscopy to quantify chemical elements. Ratios of carbon to nitrogen and calcium to phosphorus were calculated. Data were analyzed using the U-Mann–Whitney test, with р < 0.05 as a significant value.

Results. The energy dispersive X-spectrometry results confirmed morphological analysis findings by quantitatively and qualitatively assessing implants surface chemical composition. The key elements were evaluated, relevant for identifying bone tissue components like collagen (C and N) and hydroxyapatite (Ca and P), as well as implant coatings (Ti, Al, Ca, and P). Carbon and phosphorus showed fluctuations over time, with notable differences among groups. Aluminum appeared stable in some groups but varied in others. Calcium levels remained low initially and increased steadily in hydroxyapatite coated implants. Titanium levels were high initially, decreasing slightly over time. Morphological analysis correlated with surface roughness measurements. Notably, fibrin, collagen, and bone tissue presence varied among groups over time, with some groups showing significant mineralized bone tissue accumulation. After four weeks, blood clots persisted in some groups, while others exhibited bone tissue remodeling with the presence of osteoblasts and osteoclasts. Alumina-based coatings showed signs of degradation, with alumina cement scales found among macrophages and fibers.

Conclusions. Our study found that stable bone implants outperform alumina-composite coatings in long-term osseointegration due to mechanical stability. Although ceramic composites initially enhance osteoinductive properties, better attachment to titanium substrates is needed.

Clinical-pathogenetic and prognostic value of the nitrotyrosine level in the blood serum of patients with coronavirus disease (COVID-19) with pneumonia

O. V. Riabokon — 2024-08-30

The aim of the research is to determine the clinical-pathogenetic and prognostic value of nitrotyrosine levels in the blood serum of patients with COVID-19 with pneumonia in the development of oxygen dependence and the risk of fatal outcome.

Materials and methods. 123 patients with COVID-19 with pneumonia were examined, who were examined and treated according to the Order of the Ministry of Health of Ukraine dated March 28, 2020 No. 722. Patients were divided into groups: I group – 32 patients with a moderate course without oxygen dependence; II group – 91 patients with a severe course with the presence of oxygen dependence. Patients in the II group were additionally divided into subgroups: II-A subgroup – 45 patients who recovered; II-B subgroup – 46 patients who died. The content of nitrotyrosine (Hycult Biotech, the Netherlands) was determined in the blood serum by the immunoenzymatic method. Statistical data processing was carried out in the program Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J).

Results. The content of nitrotyrosine in the blood serum of patients with COVID-19 with pneumonia in a severe course with the development of oxygen dependence is higher (p < 0.001) than in patients with a moderate course of the disease without signs of oxygen dependence. The level of its increase has an inverse correlation with the oxygen saturation index (r = -0.53, р < 0.05). When hospitalized for 9.0 [7.0; 12.0] day of the disease, under the condition of nitrotyrosine level >481.97 nmol/ml (AUC = 0.909, p < 0.001), the probability of developing oxygen dependence is significant. And under the conditions of nitrotyrosine level >521.96 nmol/ml during this observation period, the probability of a fatal outcome of the disease is significant (AUC = 0.842, p < 0.001). The established correlations confirm the clinical-pathogenetic role of nitrotyrosative stress in the development of the “cytokine storm” and multiorgan failure. The content of nitrotyrosine correlates with the level of C-reactive protein (r = +0.25, p < 0.05), the ratio of absolute neutrophil count to absolute lymphocyte count (r = +0.26, p < 0.05), alanine aminotransferase activity (r = +0.26, p < 0.05) and glomerular filtration rate (r = -0.27, p < 0.05). The diagnostic value of determining the level of nitrotyrosine in predicting the course of COVID-19 with pneumonia against the background of treatment after 7 days lies in the possibility of predicting the probability of a fatal outcome of the disease. Namely, the preservation of the level of nitrotyrosine >507.98 nmol/ml (AUC = 0.681, p < 0.001) during the specified period of observation indicates a high probability of a fatal outcome of the disease.

Conclusions. In patients with COVID-19 with pneumonia, the level of nitrotyrosine elevation in the blood serum depends on the appearance of oxygen dependence and the outcome of the disease. The highest level of nitrotyrosine is in patients with COVID-19 with pneumonia with a severe course, and the degree of increase of this indicator has diagnostic value in predicting the probability of an unfavorable disease course.

Morphological and morphometric indicators of structural components of the exocrine part of the pancreas after withdrawal of administration of monosodium glutamate to rats

Yu. V. Lytvak — 2024-08-30

The aim of the study was to determine the morphological and morphometric features of structural changes in the components of the exocrine part of the pancreas of male rats after withdrawal of the food additive sodium glutamate and their transfer to a normal diet.

Materials and methods. 4 series of experiments were conducted. The 1^st series – male rats were given 70 mg/kg of sodium glutamate daily for 8 weeks to enhance their taste; the 2^nd series – rats were transferred to a standard diet 8 weeks after the use of monosodium glutamate and withdrawn from the experiment after 8 weeks (at week 16); the 3^rd series – control group rats up to 8 weeks, the 4^th series – control rats up to 16 weeks of the experiment. The pancreas was examined morphologically with morphometric analysis after the rats were withdrawn from the experiment, the material was paraffin-embedded and sections were made, stained with hematoxylin and eosin and azan.

Results. In the 1^st and 2^nd series of the experiment, atrophic and degenerative changes of the acini were preserved, which were discomposed due to edema of the organ, and had small sizes. Connective tissue and areas of adipose tissue, diffuse and focal infiltrates were visualized between the lobules and around the lobular ducts. The ducts were dilated. As in the 1^st series, there was edema of the organ parenchyma, vessel walls and ducts with fluid leakage into the intercalated spaces, and exocrinocyte apoptosis. The morphometric study of the exocrine part of the pancreas revealed that the average size of acini was statistically significantly reduced in the 1st and 2nd experimental series by 1.4 and 1.6 times, and the area by 1.2 and 1.5 times compared to control animals of the 3^rd and 4^th series. In the 1^st and 2^nd series, acini ranging in size from 71 μm to 90 μm prevailed, accounting for 38 % and 34 %, respectively, in the 1^stand 2^nd control series – 91–100 μm (46 % and 42 %) and from 111 μm to 149 μm (36 % and 38 %), respectively. In the study of the number of cells in acini in the 1^st series, exocrinocytes were present in the amount of 5.52 ± 0.58 vs. control 8.05 ± 0.32 (p < 0.001), in the 2^nd series – 5.24 ± 0.47 vs. control 7.33 ± 0.43 (p < 0.001) The area of exocrinocytes in the 2^nd series 61.95 ± 1.91 μm² vs. 78.99 ± 0.98 μm² (p < 0.05) were reduced. The diameter of the insertional, intra-lobular and inter-lobular ducts was enlarged.

Conclusions. After 8 weeks of feeding rats with monosodium glutamate and after its withdrawal and transfer of rats to the standard diet of the rat vivarium in the next 8 weeks, no improvement in the state of the pancreas was recorded, which was confirmed by morphological and morphometric studies.

Dynamics of enzymatic and glutathione link of antioxidant protection of the liver of rats of different age in case of experimental cranioskeletal injury

Yu. I. Sushko — 2024-08-30

Aim. To determine the peculiarities of enzymatic and glutathione link of antioxidant protection of the liver of rats of different age in case of experimental cranioskeletal injury.

Materials and methods. Cranioskeletal trauma (CST) was modelled in rats of three age groups (sexually immature, sexually mature, old) under thiopental sodium anesthesia. Rats were removed from the experiment under anesthesia after 3 and 7 days of the post-traumatic period. Superoxide dismutase and catalase activity, as well as glutathione peroxidase (GP) and glutathione reductase (GR) activity and the content of reduced glutathione were determined in the liver homogenate extract.

Results. It was identified that, regardless of age, under the influence of CST, after 3 and 7 days of the post-traumatic period, in the liver of experimental rats, indicated parameters of enzymatic and glutathione link of antioxidant protection significantly decrease. However, the degree of decrease of the studied indicators is significantly greater in old rats, in particular after 7 days: according to catalase activity – on 30.8 % compared to sexually immature rats and on 27.0 % compared to sexually mature rats; according to glutathione peroxidase activity – on 31.6 % compared to sexually immature rats and on 23.5 % compared to sexually mature rats; according to glutathione reductase activity – on 22.0 % compared to sexually mature rats. The obtained results indicate a systemic pro-oxidant effect of the modelled injury on organs which are distant from the site of direct injury, as well as a decrease in the antioxidant capacity of the liver of rats with increasing age.

Conclusions. Under the influence of CST, the activity of the enzyme and glutathione link of antioxidant protection of the liver gradually decreases after 3 and 7 days in experimental rats, regardless of age. Under the conditions of CST modeling, the antioxidant capacity of the liver of old rats is lower than that of sexually mature and immature rats.

Cancer metastasis of an unknown primary location into a postoperative kelody scar after a mine blast wound of the neck

O. O. Kovalyov — 2024-08-30

The connection between military trauma and cancer is not sufficiently studied. We present a clinical observation of metastasis of cancer of unknown primary localization into a keloid scar of the neck, which occurred after surgical treatment of a wound due to a previously suffered mine-explosive injury. There are no similar descriptions in the literature.

The aim of this article is analysis of a clinical case of adenocarcinoma metastases in keloid scar tissue, which occurred after gunshot wounds to the body.

Clinical observation. A young man, a military serviceman, developed a keloid scar after a landmine-explosive wound and primary surgical treatment of a neck wound, in which 2 years after excision, a metastasis of intestinal-type adenocarcinoma was detected (Cytokeratin-20+, Cytokeratin-7-, CDX-2+ and SATB 2+). With the help of clinical, endoscopic and radiological methods (computed tomography and positron emission tomography / computed tomography), the primary tumor and additional metastases in the neck, chest, abdominal cavity and pelvis could not be detected. The article analyzes the possible mechanisms of the rare case of metastasis of adenocarcinoma in the tissue of an uninfected keloid scar and discusses the concept of the formation of a premetastatic niche in the early stages of carcinogenesis of a preclinical tumor.

Conclusions. This observation raises new questions for fundamental and translational studies of the process of hematogenous metastasis during the parallel progression of the primary tumor and its metastases.

Pathogenetic links between cognitive impairment in arterial hypertension and anatomical and functional characteristics of hippocampal morphology and blood supply (a literature review)

A. O. Svitlytskyi — 2024-08-30

Aim. To update the study on morphological changes in the hippocampal structure and blood supply in conditions of persistent arterial hypertension with a focus on the cognitive sphere state.

Materials and methods. The authors independently searched and selected scientific literature for a systematic review in the PubMed, Scopus, and Cochrane databases using the following keywords “arterial hypertension”, “cognitive functions”, “morphological and functional state of the hippocampus” in full-text articles in English and Ukrainian based on the study results with a level of evidence I–III.

Results. The authors have conducted a systematic review of articles and scientific publications in PubMed, Scopus and Cochrane databases. The information of the hippocampal structure, blood supply, functions and importance for the generation of human cognitive performance in health and in conditions of persistent arterial hypertension has been processed.

Conclusions. The current research results allow asserting that the hippocampus plays an important role in combining environmental signals and creating an integral and unified perception in the spatial and temporal domains. The performance efficiency depends on cellular signaling and stability, adequate blood supply, neurotransmitter balance, and the character of a receptor landscape. Experimental studies and clinical observations show cerebral arteriole reconstruction and constriction as well as decreased NO bioavailability in the hippocampus induced by chronic arterial hypertension to compensate for excessive pressure and increased blood flow pulsatility and to protect microvessels from damage. Increased vasoconstriction results in hypoperfusion and neuronal damage, which is most obvious in the hippocampal CA1 and CA3 areas and visualized as a reduced number of chaotically scattered cells with cytoplasmic vacuoles, nuclear pyknosis and nucleolysis.

The role of mesenchymal stem cells in peripheral nerve regeneration

N. M. Nevmerzhytska — 2024-08-30

Taking into account the imperfect results of treatment of peripheral nerve injuries and despite the large number of already performed clinical and experimental studies on the regeneration of peripheral nerves, the search for new effective methods of treatment of this pathology remains relevant until now. Cell therapy is one of the innovative and promising therapeutic approaches in the field of nerve regeneration. Mesenchymal stem cells (MSCs) were first introduced in 1966 by Friedenstein and colleagues. This is a class of multipotent stem cells of mesodermal origin, which have low immunogenicity, but high capacity for self-renewal and multidirectional differentiation potential. They were found in almost all tissues. According to the International Society for Cell Therapy (ISCT, Vancouver, Canada), human MSCs express CD73, CD105, CD90 and lack hematopoietic stem cell markers (CD34, CD14, CD45, CD11b, CD79a, and HLA-DR).

There is no consensus regarding the main mechanism of action of MSCs in stimulating nerve regeneration, but in general, most likely, they perform a trophic function, inhibit proapoptotic pathways and enhance the intrinsic regenerative capacity of the nerve. The ability of MSCs to produce various immunoregulatory factors is also known, which leads to the reduction of an inadequate inflammatory response after nerve damage. MSCs can transdifferentiate into Schwann cells, acquire a Schwann-like phenotype, or stimulate the activity of endogenous Schwann cells, which are one of the key regulators of reparative nerve regeneration. MSCs also take part in the remyelination of damaged nerves due to the synthesis and release of myelin proteins MBP or P0. MSCs create an enhanced neuroprotective microenvironment that prevents nerve degeneration, supports axon growth, neurogenesis, and cellular metabolism. The property of stem cells to produce neurotrophic factors is also well known. It is interesting to note that endogenous stem cells, including those circulating in peripheral blood, are much less studied. A detailed study of various pharmacological, gene-modifying, or biomodifying methods of endogenous stem cell mobilization, their properties, and identification may be promising in regenerative medicine in general and peripheral nerve regeneration in particular.